The very small study reviewed here found that BSI-201, an experimental targeted therapy medicine, makes chemotherapy work better against aggressive forms of breast cancer. These results confirm findings from earlier studies. These results were reported at the 2009 San Antonio Breast Cancer Symposium.
DNA carries genetic information in both healthy and cancer cells. Chemotherapy medicines work against cancer by damaging the DNA or blocking DNA reproduction. But all cells can fix DNA damage caused by chemotherapy medicines. So sometimes cancer cells may not respond or stop responding to a chemotherapy medicine. When cancer stops responding to a treatment, it's called "treatment resistance."
BSI-201 is a PARP inhibitor. The PARP (poly ADP-ribose polymerase) enzyme fixes DNA damage in cells, including DNA damage caused by chemotherapy medicines. Scientists developed PARP inhibitors based on the idea that a medicine that interferes with or inhibits the PARP enzyme might make it harder for cancer cells to fix damaged DNA, which would make it harder for cancer to become resistant to chemotherapy.
In the study reviewed here, 123 women diagnosed with advanced-stage, triple-negative (HER2-negative, estrogen-receptor-negative, progesterone-receptor-negative) breast cancer were treated with a combination of two standard chemotherapy medicines: gemcitabine (brand name: Gemzar) and carboplatin (brand name: Paraplatin). Half of the women also received BSI-201. All of the women had received a variety of other cancer treatments before this study.
The women who got the two chemotherapy medicines plus BSI-201:
Women who got BSI-201 plus chemotherapy had the same types and severity of side effects as the women who got only chemotherapy.
While this study is promising, BSI-201 is considered an experimental treatment. More research is needed before doctors completely understand how and when to use PARP inhibitors to treat breast cancer.
If you're being treated for advanced-stage breast cancer, you and your doctor may be considering a number of treatment options, especially if the cancer has stopped responding to standard treatments. If you're willing to participate in a clinical trial, you may have even more options available, possibly including a PARP inhibitor. Talk to your doctor about clinical trials that might be a good fit for you and your unique situation. Visit the Breastcancer.org Clinical Trials pages for more information.
Stay tuned to Breastcancer.org Research News to learn about the latest research on new, better ways to more effectively treat breast cancer.
SAN ANTONIO (MedPage Today) -- Treatment with a drug that inhibits DNA repair in cancer cells improved breast cancer patients' survival by almost 60% when added to conventional chemotherapy, according to results from an ongoing study.
Patients who received the investigational drug BSI-201 in addition to chemotherapy had a median survival of 12.2 months compared with 7.7 months for chemotherapy alone. The survival benefit came with no added toxicity, Joyce O'Shaughnessy, MD, of Baylor Sammons Cancer Center in Dallas, reported at the San Antonio Breast Cancer Symposium.
"The results were spectacular," said Peter Ravdin, MD, of the University of Texas Health Science Center at San Antonio and a member of the symposium program committee.
"Previously reported data from the study showed a 16% response rate with chemotherapy, which is what one would expect," he added during an interview.
"The response rate with the PARP inhibitor was 48%, quite a striking difference. In addition, the responses lasted longer, three months with chemotherapy and seven months in patients treated with the combination."
"In many instances, increased response rates do not translate into increased survival," said Ravdin, who was not involved with the study. "In this case it did, and the survival difference was quite striking."
The findings confirm and extend results reported at the American Society of Clinical Oncology meeting, when survival was more than nine months with BSI-201 plus chemotherapy, versus less than six months with chemotherapy alone.
BSI-201 is the first of a new class of agents that inhibit cancer cells' DNA-repair mechanisms. BSI-201 inhibits the nuclear enzyme PARP1, which is involved in multiple cellular processes, including DNA repair, O'Shaughnessy and colleagues said in a poster presentation.
The enzyme is upregulated in primary breast cancer and other types of cancer.
Clinical studies have shown that BSI-201 enhances chemotherapy-induced DNA damage, and the agent has proven to be safe and well tolerated when combined with several different chemotherapy regimens (ASCO 2009, Abstract 3579).
Preclinical studies have suggested that combining a PARP inhibitor with gemcitabine (Gemzar) and with platinum agents leads to additive therapeutic activity.
O'Shaughnessy and colleagues reported findings from a Phase II study to determine whether adding BSI-201 to gemcitabine/carboplatin chemotherapy would increase the clinical benefit, compared with chemotherapy alone, in patients with triple-negative breast cancer (estrogen-receptor, progesterone-receptor, and HER2 negative).
The analysis involved 123 patients who received gemcitabine and carboplatin and were randomized to BSI-201 or no additional therapy.
The patients' age was in the mid-50s, and most had ECOG 0 performance status. Most of the patients had more than one metastatic site. About 60% had received neoadjuvant systemic therapy, while about a third had received one or two therapies for metastatic disease, and more than half had prior exposure to a taxane and an anthracycline.
The survival difference translated into a hazard ratio of 0.50 in favor of the BSI-201 arm (95% CI 0.30 to 0.82, P=0.005).
The frequency of hematologic and nonhematologic adverse events did not differ significantly between treatment groups. The conventional chemotherapy accounted for most of the toxicity, researchers said.
The study was supported by sanofi-aventis.
The authors reported no disclosures.
Primary source: San Antonio Breast Cancer Symposium Source reference: O'Shaughnessy J, et al "Updated results of a randomized phase II study deonstrating efficacy and safety of BSI-201, a PARP inhibitor, in combination with gemcitabine/carboplatin in metastatic triple-negative breast cancer" SABCS 2009; Abstract 3122.
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